Rare events and first passage time statistics from the energy landscape

We analyze the probability distribution of rare first passage times corresponding to transitions between product and reactant states in a kinetic transition network. The mean first passage times and the corresponding rate constants are analyzed in detail for two model landscapes and the double funnel landscape corresponding to an atomic cluster. Evaluation schemes based on eigendecomposition and kinetic path sampling, which both allow access to the first passage time distribution, are benchmarked against mean first passage times calculated using graph transformation. Numerical precision issues severely limit the useful temperature range for eigendecomposition, but kinetic path sampling is capable of extending the first passage time analysis to lower temperatures, where the kinetics of interest constitute rare events. We then investigate the influence of free energy based state regrouping schemes for the underlying network. Alternative formulations of the effective transition rates for a given regrouping are compared in detail to determine their numerical stability and capability to reproduce the true kinetics, including recent coarse-graining approaches that preserve occupancy cross correlation functions. We find that appropriate regrouping of states under the simplest local equilibrium approximation can provide reduced transition networks with useful accuracy at somewhat lower temperatures. Finally, a method is provided to systematically interpolate between the local equilibrium approximation and exact intergroup dynamics. Spectral analysis is applied to each grouping of states, employing a moment-based mode selection criterion to produce a reduced state space, which does not require any spectral gap to exist, but reduces to gap-based coarse graining as a special case. Implementations of the developed methods are freely available online.